Prospective Role of MicroRNAs in Depression.
Depression is a debilitating disease that is affecting a growing number of patients, both physically and mentally. In addition to mood changes, depression results in cognitive impairment. Although depression studies have been going on for decades, the underlying mechanism still remains unclear. MicroRNAs (miRNAs), a type of small non-coding RNAs, predominantly control the expression of their target mRNAs to exert their functions. Some evidences have revealed the importance of miRNAs in the mechanism of depression,however, these studies are still in their infancy. Alterations in brain regions, synaptic plasticity, hypothalamic-pituitary-adrenal (HPA) axis, changes in the levels of serotonin and glucocorticoids, together with stress response have been proven to be involved in depression. These alterations can influence cognition, learning and memory, with recent evidences demonstrating the involvement of miRNAs in several aspects of stress response, neural plasticity and neurogenesis as well as pathogenesis of depression. In light of these theories of depression, this review was aimed at elucidating the role of miRNAs in the underlying mechanisms of depression resulting in cognitive, learning and memory impairments. Both PubMed and Scopus databases were employed in scouring for research reports pertaining to this area of study. A total of 180 articles were obtained from these two databases. With the probing of classical theories of depression as well as the connection between miRNAs and depression, more studies,nevertheless, are needed to ascertain the full mechanism of depression along with its resultant cognitive, learning and memory impediments.


The structure and ultrastructure of the rostral cartilage in the spiny eel, Macrognathus siamensis (Teleostei: Mastacembeloidei).
An elastic, cell-rich cartilage provides flexible support to the highly mobile, rostral tentacle of the mastacembelid, Macrognathus siamensis. Active movement of the tentacle is effected by skeletal muscles, the muscular bellies of which are located outside the organ. The tentacle returns to its original shape by elastic recoil. The cartilage resembles plant supporting tissue and the cartilages of certain invertebrates. It is surrounded by a thick perichondrium and articulates at a synovial joint with the supraethmoid. The chondrocytes are large and shrunken within lacunae. They contain glycogen and cytoplasmic stores of RNA. The matrix is reduced to thin seams between adjacent cells, and stains strongly with alcian blue and a variety of elastic stains. Parts of the matrix are trilaminar, and such an appearance recalls the distinction between the primary cell walls of adjacent plant cells and the intervening middle lamella. The perichondrium consists of an alternating sequence of cells, circularly arranged collagen fibres and a foamy, amorphous material of unknown composition. Deep to the perichondrium, the chondrocytes are packed with intermediate filaments. Membrane-bound organelles are not prominent, though mitochondria are located at the periphery of the cell. The ultrastructural similarities between these chondrocytes and those of hyaline-cell cartilage (chondroid) support the contention that Schaffer's concept of a rigid distinction between 'true' cartilage and 'chondroid' is no longer tenable. The matrix is devoid of collagen and is most distinctive. In the immediate vicinity of the cells it consists of matrix granules and matrix fibers but, where a trilaminar appearance is easily discernible, there is a central zone that consists of large masses of amorphous material that is presumed to contain elastin. Such amorphous material has not previously been seen in any teleostean elastic tissue. By contrast, elastic system fibres, readily demonstrable elsewhere in teleosts, are conspicuously absent.


A Novel Experience Sampling Method Tool Integrating Momentary Assessments of Cognitive Biases: Two Compliance, Usability, and Measurement Reactivity Studies.
Experience sampling methods (ESMs) are increasingly being used to study ecological emotion dynamics in daily functioning through repeated assessments taken over several days. However, most of these ESM approaches are only based on self-report assessments, and therefore, studies on the ecological trajectories of their underlying mechanisms are scarce (ie, cognitive biases) and require evaluation through experimental tasks. We developed a novel ESM tool that integrates self-report measures of emotion and emotion regulation with a previously validated app-based cognitive task that allows for the assessment of underlying mechanisms during daily functioning. The objective of the study is to test this new tool and study its usability and the possible factors related to compliance with it in terms of latency and missing responses. Among the compliance predictors, we considered psychological and time-related variables, as well as usability, measurement reactivity, and participants' satisfaction with the tool. We conducted 2 extensive ESM studies-study 1 (N=84; a total of 3 assessments per day for 5 days) and study 2 (N=135; a total of 3 assessments per day for 10 days). In both studies, participants found the tool highly usable (average usability score >81). By using mixed regression models, we found both common and specific results for the compliance predictors. In both study 1 and study 2, latency was significantly predicted by the day (P<.001 and P=.003, respectively). Participants showed slower responses to the notification as the days of the study progressed. In study 2 but not in study 1, latency was further predicted by individual differences in overload with the use of the app, and missing responses were accounted for by individual differences in stress reactivity to notifications (P=.04). Thus, by using a more extensive design, participants who experienced higher overload during the study were characterized by slower responses to notifications (P=.01), whereas those who experienced higher stress reactivity to the notification system were characterized by higher missing responses. The new tool had high levels of usability. Furthermore, the study of compliance is of enormous importance when implementing novel ESM methods, including app-based cognitive tasks. The main predictors of latency and missing responses found across studies, specifically when using extensive ESM protocols (study 2), are methodology-related variables. Future research that integrates cognitive tasks in ESM designs should take these results into consideration by performing accurate estimations of participants' response rates to facilitate the optimal quality of novel eHealth approaches, as in this study.


Improved donor lung size matching by estimation of lung volumes based on chest X-ray measurements.
Organ size matching is an important determinant of successful allocation and outcomes in lung transplantation. While computed tomography (CT) is the gold standard, it is rarely used in an organ-donor context, and chest X-ray (CXR) may offer a practical and accurate solution in estimating lung volumes for donor and recipient size matching. We compared CXR lung measurements to CT-measured lung volumes and traditional estimates of lung volume in the same subjects. Our retrospective study analyzed clinically obtained CXR and CT lung images of 250 subjects without evidence of lung disease (mean age 9.9 ± 7.8 years; 129 M/121F). From CT, each lung was semi-automatically segmented and total lung volumes were quantified. From anterior-posterior CXR view, each lung was manually segmented and areas were measured. Lung lengths from the apices to the mid-basal regions of each lung were measured from CXR. Quantified CT lung volumes were compared to the corresponding CXR lung lengths, CXR lung areas, height, weight, and predicted total lung capacity (pTLC). There are strong and significant correlations between CT volumes and CXR lung areas in the right lung (R2 = .89, p < .0001), left lung (R2 = .87, p < .0001), and combined lungs (R2 = .89, p < .0001). Similar correlations were seen between CT volumes and CXR measured lung lengths in the right lung (R2 = .79, p < .0001) and left lung (R2 = .81, p < .0001). This correlation between anatomical lung volume (CT) and CXR was stronger than lung-volume correlation to height (R2 = .66, p < .0001), weight (R2 = .43, p < .0001), or pTLC (R2 = .66, p < .0001). CXR measures correlate much more strongly with true lung volumes than height, weight, or pTLC. The ability to obtain efficient and more accurate lung volume via CXR has the potential to change our current listing practices of using height as a surrogate for lung size, with a case example provided.


Increase levels of apo-A1 and apo B are associated in knee osteoarthritis: lack of association with VEGF-460 T/C and +405 C/G polymorphisms.
To investigate the genotype and allele frequency of vascular endothelial growth factor gene polymorphisms in knee osteoarthritis (OA) and their relationship with disease activity and lipid profile, we enrolled 49 knee OA patients and 75 healthy subjects (HS) as a control group. Body mass index (BMI), laboratorial assessment and genotyped by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) were studied in both groups. Disease activity was determined using Lequesne and WOMAC indexes; a P value<0.05 was considered significant. The -460 and +405 VEGF polymorphisms did not shown significant association between OA patients and HS. However, between OA patients and HS a significant differences were observed in BMI, age, apo A-I and apo B, independently of both polymorphisms studied (P<0.05). In conclusion, increased apo A-1 and apo B levels are associated in knee OA, but the -460 T/C and +405 C/G VEGF polymorphisms are not associated with knee OA susceptibility.


Prepubertal growth and single nucleotide polymorphism analysis of the growth hormone gene of low birth weight Holstein calves.
Holstein calves weighing less than 20 kg at birth have been noted in Korea. Due to insufficient information, we raised small calves with age-matched normal birth weight Holstein calves and determined body weights before puberty. In addition, 3 single nucleotide polymorphisms (SNPs) of the growth hormone (GH) gene were analyzed. Up to 10 months of age, low birth weight calves were smaller than normal weight calves. In exon 5 of the GH gene, SNP genotype variation was detected in some small calves; however, this did not appear to be the only factor inducing low birth weight and slow growth.


Optimized Ultrasonic Irradiation Finds Out Ultrastable Aβ1-40 Oligomers.
Oligomer species of amyloid β (Aβ) peptides are intensively investigated because of their relevance to Alzheimer's disease (AD), and a stable oligomer will be a cause of AD. In this article, we investigate the structural stability of two representative Aβ1-40 oligomers, which are with and without the β-sheet structure, denoted by β and non-β oligomers, respectively, using optimized ultrasonic irradiation (OUI). Recent studies reveal that OUI significantly accelerates the fibril formation in Aβ1-40 monomers; it is capable of transforming any unstable oligomers into fibrils (the dead-end products) in a short time. First, we find that β oligomers can be produced under high-speed stirring agitation; their β-sheet structures are evaluated by the circular-dichroism spectrum measurement, by the immunoassay using the fibril-specific OC antibody, and by the seeding experiment, showing identical characteristics to those formed in previous reports. Second, we form non-β oligomers in a high-concentration NaCl solution and confirm that they include no β-sheet structure, and they are recognized by the oligomer-specific A11 antibody. Furthermore, we confirm the neurotoxicity of the two types of oligomers using the neural tissue derived from mouse embryonic stem cells. We apply the OUI agitation to the β and non-β oligomers. The non-β oligomers are transformed into the fibrils, indicating that they are intermediate species in the fibrillation pathway. However, the β oligomers are surprisingly unaffected by OUI, indicating their high thermodynamic stability. We conclude that the β oligomers should be the independent dead-end products of another pathway, different from the fibrillation pathway.


The scope and direction of health informatics.
Health Informatics (HI) is a dynamic discipline based on the medical sciences, information sciences, and cognitive sciences. Its domain can broadly be defined as medical information management. The purpose of this paper is to provide an overview of this domain, discuss the current "state of the art," and indicate the likely growth areas for health informatics. The sources of information used in this paper are selected publications from the literature of Health Informatics, HI 5300: Introduction to Health Informatics, which is a course from the Department of Health Informatics at the University of Texas Houston Health Sciences Center, and the author's personal experience in practicing telemedicine and implementing an electronic medical record at the NASA-Johnson Space Center. The conclusion is that the direction of Health Informatics is in the direction of data management, transfer, and representation via electronic medical records and the Internet.


Expression Divergence of Chemosensory Genes between Drosophila sechellia and Its Sibling Species and Its Implications for Host Shift.
Drosophila sechellia relies exclusively on the fruits of Morinda citrifolia, which are toxic to most insects, including its sibling species Drosophila melanogaster and Drosophila simulans. Although several odorant binding protein (Obp) genes and olfactory receptor (Or) genes have been suggested to be associated with the D. sechellia host shift, a broad view of how chemosensory genes have contributed to this shift is still lacking. We therefore studied the transcriptomes of antennae, the main organ responsible for detecting food resource and oviposition, of D. sechellia and its two sibling species. We wanted to know whether gene expression, particularly chemosensory genes, has diverged between D. sechellia and its two sibling species. Using a very stringent definition of differential gene expression, we found a higher percentage of chemosensory genes differentially expressed in the D. sechellia lineage (7.8%) than in the D. simulans lineage (5.4%); for upregulated chemosensory genes, the percentages were 8.8% in D. sechellia and 5.2% in D. simulans. Interestingly, Obp50a exhibited the highest upregulation, an approximately 100-fold increase, and Or85c--previously reported to be a larva-specific gene--showed approximately 20-fold upregulation in D. sechellia. Furthermore, Ir84a (ionotropic receptor 84a), which has been proposed to be associated with male courtship behavior, was significantly upregulated in D. sechellia. We also found expression divergence in most of the chemosensory gene families between D. sechellia and the two sibling species. Our observations suggest that the host shift of D. sechellia was associated with the enrichment of differentially expressed, particularly upregulated, chemosensory genes.


High resolution hard x-ray microscope on a second generation synchrotron source.
A full-field, transmission x-ray microscope (TXM) operating in the energy range of 7-11 keV has been installed at the U7A beamline at the National Synchrotron Radiation Laboratory, a second generation synchrotron source operating at 0.8 GeV. Although the photon flux at sample position in the operating energy range is significantly low due to its relatively large emittance, the TXM can get high quality x-ray images with a spatial resolution down to 50 nm with acceptable exposure time. This TXM operates in either absorption or Zernike phase contrast mode with similar resolution. This TXM is a powerful analytical tool for a wide range of scientific areas, especially studies on nanoscale phenomena and structural imaging in biology, materials science, and environmental science. We present here the property of the x-ray source, beamline design, and the operation and key optical components of the x-ray TXM. Plans to improve the throughput of the TXM will be discussed.


Nucleosomes associated with newly replicated DNA have an altered conformation.
In vitro DNA synthesis was studied in HeLa cell nuclei, with emphasis on the question of whether newly replicated DNA is associated with nucleosomes. The newly replicated DNA was twice as sensitive to digestion by micrococcal nuclease as mature chromatin DNA, reaching a limit digest at 20-25% acid-insoluble product. Examination of the intermediates of digestion by micrococcal nuclease showed the nuclease-resistant, new DNA to be complexed in nucleosomes. However, structural differences were evident at both the polynucleosomal and the core particle level. The nucleosomes on newly replicated DNA were arranged with a repeat size of 165-170 base pairs-i.e., smaller than the 185-base-pair repeat of mature chromatin. The heterogeneity of polynucleosomal multimers, evident in digests of whole chromatin, was reduced in newly replicated chromatin such that the multimers resolved as sharply defined bands. Nucleosomal core particles associated with newly replicated DNA had a different conformation from particles in mature chromatin based on the following lines of evidence: (i) during micrococcal nuclease digestion, the monomer nucleosomes did not accumulate but were rapidly degraded under certain conditions; (ii) micrococcal nuclease limit digest patterns and DNase I digestion patterns, both of which reflect internal nucleosomal protein DNA associations, differed significantly from control patterns. These findings bear directly on models postulated for nucleosome-DNA interactions during chromation replication. A possible mechanism to account for the conformational change and its role in replication are discussed.


The role of speech-specific properties of the background in the irrelevant sound effect.
The irrelevant sound effect (ISE) is the finding that serial recall performance is impaired under complex auditory backgrounds such as speech as compared to white noise or silence. Several findings have demonstrated that ISE occurs with nonspeech backgrounds and that the changing-state complexity of the background stimuli is critical to ISE. In a pair of experiments, we investigate whether speech-like qualities of the irrelevant background have an effect beyond their changing-state complexity. We do so by using two kinds of transformations of speech with identical changing-state complexity: one kind that preserved speech-like information (sinewave speech and fully reversed sinewave speech) and others in which this information was distorted (two selectively reversed sinewave speech conditions). Our results indicate that even when changing-state complexity is held constant, sinewave speech conditions in which speech-like interformant relationships are disrupted, produce less ISE than those in which these relationships are preserved. This indicates that speech-like properties of the background are important beyond their changing-state complexity for ISE.


Effectiveness and cost-effectiveness of facilitated percutaneous coronary intervention compared with primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction transferred from community hospitals.
Primary percutaneous coronary intervention ([PCI], percutaneous transluminal coronary angioplasty+stenting) for ST-segment elevation myocardial infarction (STEMI) is regarded as superior to fibrinolysis even if it means that patients need to be transferred from one center to another to undergo the procedure. However, this inevitable delay between symptom onset and PCI, caused by the time required to travel, might increase the occurrence of cardiac events. A hybrid method called facilitated PCI uses fibrinolysis and/or glycoprotein (GP) IIb/IIIa inhibitors before transfer to a tertiary medical center where urgent PCI might be performed. This approach, however, has not been systematically evaluated. The purpose of this study was to compare the effectiveness (combined end point of in-hospital mortality, reinfarction, stroke, or emergency revascularization) and cost-effectiveness of utilizing a bolus thrombolytic agent with GP IIb/IIIa inhibitor followed by transfer to a tertiary institution for facilitated PCI or standard of care transfer without primary PCI drugs among patients presenting to a community hospital with STEMI. This was a prospective, single-center, cohort study comprising data from STEMI patients transferred from community hospitals to Hartford Hospital, Hartford, Connecticut, from the years 2000 to 2003. At the time of analysis, patients receiving primary PCI were matched (1:1) with those receiving facilitated PCI, utilizing propensity scores to assure similar demographics. The combined incidence of major adverse cardiac end points (MACE) and total hospital costs was compared between groups. Non-parametric bootstrapping was conducted to calculate CIs for the incremental cost-effectiveness ratio and generate a quadrant analysis. Based on 254 propensity score-matched patients (127 facilitated PCI and 127 primary PCI), in-hospital MACE and total hospital costs were reduced by 61.3% and US 4563 dollars (2005), respectively, in patients receiving facilitated compared with primary PCI (P=0.021 and P=NS, respectively). Patients receiving facilitated PCI were more likely to have target lesion Thrombolysis in Myocardial Infarction (TIMI) III (normal) blood flow on cardiac catheterization than those receiving primary PCI (49.6% vs 30.7%; P=0.002). However, the rate of TIMI bleeding was similar in both groups (21.3% in the facilitated PCI group vs 18.9% in the primary PCI group). Nonsignificant reductions were observed in both intensive care unit (ICU) and total length of stay (LOS) (0.8 day and 1.0 day, respectively) compared with the primary PCI group. Bootstrap analysis revealed that of 25,000 samplings, facilitated PCI would likely be both more effective and less costly 94.6% of the time. The use of facilitated PCI in STEMI patients who initially presented to community hospitals and were transferred for PCI appeared to significantly reduce the incidence of MACE, and increase the likelihood of having baseline TIMI III blood flow at time of catheterization. Nonsignificant reductions were observed in total ICU and hospital LOS. However, there did not appear to be a significant effect on the incidence of bleeding in patients receiving facilitated PCI. Bootstrap analysis confirmed that facilitated PCI would be both a more effective and less costly strategy.


Acute Spinal Subdural Hematoma after Vertebroplasty: A Case Report Emphasizing the Possible Etiologic Role of Venous Congestion.
Study Design Case report and literature review. Objective Spinal subdural hematomas are rare events that often progress with severe neurologic deficits. Although there have been several case reports in the literature of spontaneous spinal subdural hematomas in the setting of anticoagulation, antiplatelet therapy, or coagulation disorders, the exact pathophysiology of such phenomena remains obscure. Methods We present the first report of a subdural hematoma after a percutaneous vertebroplasty and provide a comprehensive review on the anatomy of venous drainage of the vertebral bodies with emphasis on the possible effects of venous congestion caused by cement obstruction. Results Because the subdural hematoma occurred in the absence of major cement extravasation to the spinal canal and two levels above the site of the vertebroplasty, we discuss the possible role of venous congestion as the main etiologic factor leading to rupture of the fragile, valveless radiculomedullary veins into the subdural space. Conclusions The reported case supports a possible new pathophysiological scheme for the development of spinal subdural hematoma in which venous congestion plays a pivotal etiologic role. The reported findings suggests that future anatomical and histologic studies investigating the response of the radiculomedullary veins to congestive venous hypertension may shed new light into the pathophysiology of spinal subdural hematomas.


Interactions of volatile anaesthetics with rocuronium bromide in perspective.
A review of several publications shows that there is general agreement that inhalational anaesthetic agents potentiate the neuromuscular effects of rocuronium in the same order as other similar agents, namely; enflurane and isoflurane > halothane > intravenous anaesthetics. However, such potentiation is not evident during induction and only becomes significant as anaesthesia becomes more prolonged. It is manifest as a prolongation in the duration of action of maintenance doses and a decrease in the recovery rate. During long-lasting procedures in which enflurane or isoflurane are used, smaller than usual maintenance doses or lower infusion rates should be employed.


Diagnostic and therapeutic treatment methods for intrathoracic extrapulmonary lipomas.
Lipomas are rarely seen tumors of adipose tissue that are benign in character. Although mostly located to the subcutaneous region, specifically in the upper back, neck, and shoulder, they may also occur in thoracic cavity. They aim of the study was to analyse clinical features and outcome of treatment of intrathoracic pleural lipomas. We retrospectively evaluated the clinicopathological records of seven patients with intrathoracic lipomas who had undergone surgery between 2005 and 2017. We made analyses in terms of age, gender, admission complaints, lesion locations and dimensions, diagnostic techniques, operative procedures, histopathological features, and prognosis. Four women and three men with a mean age 62.7 (range, 48-75 years) were included. They had chest pain (n = 2), effort dyspnea (n = 1) as the admission symptom, whereas four patients were asymptomatic, whose lesions were detected on chest radiography on an incidental basis. The radiological features of the tumors were well-demarcated, homogenous lesions with fat density. Tumors of all cases were excised, which were located on the right side in two patients and left in five. We used video-assisted thoracoscopy in two patients, single-port video-assisted thoracoscopy in three patients, thoracotomy in two patients. All lesions were of parietal pleural origin and were located intrathoracically. They had a range of size between 4 and 10 cm, with an average of 6.7 cm. All cases were operated with complete resection. At a mean follow-up duration of 4.7 years no recurrence was noted. Intrathoracic lipomas are rare, benignly behaving tumors. As it may prove difficult to differentiate them from malignant lesions and they may grow in an invasive growth pattern, surgery should be pursued in all patients for both diagnosis and treatment.


Genomic and Epigenomic Heterogeneity of Hepatocellular Carcinoma.
Understanding the intratumoral heterogeneity of hepatocellular carcinoma is instructive for developing personalized therapy and identifying molecular biomarkers. Here we applied whole-exome sequencing to 69 samples from 11 patients to resolve the genetic architecture of subclonal diversification. Spatial genomic diversity was found in all 11 hepatocellular carcinoma cases, with 29% of driver mutations being heterogeneous, including TERT, ARID1A, NOTCH2, and STAG2. Similar with other cancer types, TP53 mutations were always shared between all tumor regions, that is, located on the "trunk" of the evolutionary tree. In addition, we found that variants within several drug targets such as KIT, SYK, and PIK3CA were mutated in a fully clonal manner, indicating their therapeutic potentials for hepatocellular carcinoma. Temporal dissection of mutational signatures suggested that mutagenic processes associated with exposure to aristolochic acid and aflatoxin might play a more important role in early, as opposed to late, stages of hepatocellular carcinoma development. Moreover, we observed extensive intratumoral epigenetic heterogeneity in hepatocellular carcinoma based on multiple independent analytical methods and showed that intratumoral methylation heterogeneity might play important roles in the biology of hepatocellular carcinoma cells. Our results also demonstrated prominent heterogeneity of intratumoral methylation even in a stable hepatocellular carcinoma genome. Together, these findings highlight widespread intratumoral heterogeneity at both the genomic and epigenomic levels in hepatocellular carcinoma and provide an important molecular foundation for better understanding the pathogenesis of this malignancy. Cancer Res; 77(9); 2255-65. ©2017 AACR.


Modified direct-double-differential PCR for gene dosage quantification of HER2.
HER2 amplification and/or overexpression in breast cancer are adverse prognostic factors and can predict the response to trastuzumab therapy. As assessment of HER2 status in breast cancer is of great importance for clinical decision-making, it is crucial to have reliable methods to quantify HER2. In the present project, we have developed a modification of the direct-double-differential PCR method (dddPCR) for gene dosage quantification of HER2 in breast cancer samples. The study was also undertaken to establish the potential application of the newly developed dddPCR method for HER2 testing in a diagnostic laboratory. The dddPCR validity for determining HER2 amplification in comparison to IHC-based HercepTest for the detection of protein levels was performed. Modified dddPCR was proven to be highly reproducible and reliable. A statistically significant correlation between protein expression and gene dosage of HER2 was found in the examined material. The obtained results indicate that dddPCR provides a fast and reliable diagnostic tool for HER2 quantification and may be considered as a supplementary method to verify equivocal results obtained with IHC-based HercepTest. Notably, dddPCR can be performed in every basic molecular biology laboratory, and is inexpensive and time-saving.


Polycythemia vera: the current status of preclinical models and therapeutic targets.
Polycythemia vera (PV) is the most common myeloproliferative neoplasm (MPN). PV is characterized by erythrocytosis, leukocytosis, thrombocytosis, increased hematocrit, and hemoglobin in the peripheral blood. Splenomegaly and myelofibrosis often occur in PV patients. Almost all PV patients harbor a mutation in the JAK2 gene, mainly represented by the JAK2V617F point mutation. This article examines the recent in vitro and in vivo available models of PV and moreover, it offers insights on emerging biomarkers and therapeutic targets. The evidence from mouse models, resembling a PV-like phenotype generated by different technical approaches, is discussed. The authors searched PubMed, books, and clinicaltrials.gov for original and review articles and drugs development status including the terms Myeloproliferative Neoplasms, Polycythemia Vera, erythrocytosis, hematocrit, splenomegaly, bone marrow fibrosis, JAK2V617F, Hematopoietic Stem Cells, MPN cytoreductive therapy, JAK2 inhibitor, histone deacetylase inhibitor, PV-like phenotype, JAK2V617F BMT, transgenic JAK2V617F mouse, JAK2 physiologic promoter. Preclinical models of PV are valuable tools for enabling an understanding of the pathophysiology and the molecular mechanisms of the disease. These models provide new biological insights on the contribution of concomitant mutations and the efficacy of novel drugs in a 'more faithful' setting. This may facilitate an enhanced understanding of pathogenetic mechanisms and targeted therapy.


Complete Genome Sequences of Two Chikungunya Viruses Isolated in the Central African Republic in the 1970s and 1980s.
Some arboviruses threaten human global health with potentially explosive emergence. Analysis of whole-genome sequences of decades-old isolates might contribute to the understanding of the complex dynamics which drive their circulation and emergence. Here, we report the whole-genome sequences of two Chikungunya viruses isolated in the Central African Republic in the 1970s and 1980s.


Targeted disruption of the mouse gene encoding the V-ATPase accessory subunit Ac45.
Acidification of organelles of the eukaryotic vacuolar system is important for multiple intracellular processes including receptor-mediated endocytosis, proteolytic activity in lysosomes, and prohormone sorting and processing in secretory granules. Responsible for the generation of a proton gradient across a membrane is vacuolar H(+)-ATPase (V-ATPase). How the activity of this multisubunit enzyme is regulated remains to be established. Accessory subunits of the V-ATPase may be involved in the organelle-specific regulation, one candidate being the chromaffin granular V-ATPase-associated protein Ac45. To assess the function of Ac45, we disrupted its gene by gene targeting in male mouse embryonic stem cells. We have successfully generated Ac45 null mutant (-IY) embryonic stem cells and injected them into C57BL/6 recipient blastocysts. The blastocysts were replaced into pseudopregnant foster mothers, giving rise to 16 littermates. One of these appeared to be a low-chimeric female mouse that died 6 weeks after birth. No signs of late abortion were detected in the foster mothers. The results suggest that the injected Ac45 null mutant embryonic stem cells affect the normal development of the blastocyst and are in line with knockout studies on other V-ATPase subunits that point to an essential role for the V-ATPase in early embryonic development.


Interactions among predators and the cascading effects of vertebrate insectivores on arthropod communities and plants.
Theory on trophic interactions predicts that predators increase plant biomass by feeding on herbivores, an indirect interaction called a trophic cascade. Theory also predicts that predators feeding on predators, or intraguild predation, will weaken trophic cascades. Although past syntheses have confirmed cascading effects of terrestrial arthropod predators, we lack a comprehensive analysis for vertebrate insectivores-which by virtue of their body size and feeding habits are often top predators in these systems-and of how intraguild predation mediates trophic cascade strength. We report here on a meta-analysis of 113 experiments documenting the effects of insectivorous birds, bats, or lizards on predaceous arthropods, herbivorous arthropods, and plants. Although vertebrate insectivores fed as intraguild predators, strongly reducing predaceous arthropods (38%), they nevertheless suppressed herbivores (39%), indirectly reduced plant damage (40%), and increased plant biomass (14%). Furthermore, effects of vertebrate insectivores on predatory and herbivorous arthropods were positively correlated. Effects were strongest on arthropods and plants in communities with abundant predaceous arthropods and strong intraguild predation, but weak in communities depauperate in arthropod predators and intraguild predation. The naturally occurring ratio of arthropod predators relative to herbivores varied tremendously among the studied communities, and the skew to predators increased with site primary productivity and in trees relative to shrubs. Although intraguild predation among arthropod predators has been shown to weaken herbivore suppression, we find this paradigm does not extend to vertebrate insectivores in these communities. Instead, vertebrate intraguild preda-tion is associated with strengthened trophic cascades, and insectivores function as dominant predators in terrestrial plant-arthropod communities.


Revision of the genus Palmanura Cassagnau, 1983 (Collembola: Neanuridae: Neanurinae: Sensillanurini).
A revision of Palmanura is presented, P. klompeni sp. nov. P. moralesi sp. nov., P. contrerasi sp. nov. and P. axelretanai sp. nov. are described and illustrated, and P. normae Palacios-Vargas, 1996 and P. sernai Palacios-Vargas Simón Benito, 2009 are redescribed. New records and distribution data are given for several species and a key for identifying every species of the genus are included. A discussion on the ventral chaetotaxy of all genera of the tribe Sensillanurini and a comparison with other tribes of Neanurinae is also provided.


[Surgery ex situ in kidney transplantation].
123 vascular surgical procedures were performed ex situ in the course of 534 renal transplantations performed between 1982 and 1987. This study demonstrates that the elongation of the renal vein facilitates the transplantation and significantly reduces the risk of arterial stenosis and that arterial repairs, in the case of multiple arteries, constitute a reliable technique. The elongation of the renal vein means that all donor right kidneys must be procured with the infra-renal inferior vena cava. Donor kidneys with multiple arteries without patch graft can be repaired on the table in the great majority of cases.


Spin-polarized scanning tunneling microscopy with quantitative insights into magnetic probes.
Spin-polarized scanning tunneling microscopy and spectroscopy (spin-STM/S) have been successfully applied to magnetic characterizations of individual nanostructures. Spin-STM/S is often performed in magnetic fields of up to some Tesla, which may strongly influence the tip state. In spite of the pivotal role of the tip in spin-STM/S, the contribution of the tip to the differential conductance dI/dV signal in an external field has rarely been investigated in detail. In this review, an advanced analysis of spin-STM/S data measured on magnetic nanoislands, which relies on a quantitative magnetic characterization of tips, is discussed. Taking advantage of the uniaxial out-of-plane magnetic anisotropy of Co bilayer nanoisland on Cu(111), in-field spin-STM on this system has enabled a quantitative determination, and thereby, a categorization of the magnetic states of the tips. The resulting in-depth and conclusive analysis of magnetic characterization of the tip opens new venues for a clear-cut sub-nanometer scale spin ordering and spin-dependent electronic structure of the non-collinear magnetic state in bilayer high Fe nanoislands on Cu(111).


CLINICAL DECISION MAKING IN OLDER ADULTS WITH COVID-19 IN DEVELOPING COUNTRIES: LOOKING BEYOND CHRONOLOGICAL AGE.
The coronavirus disease 2019 (COVID-19) has been declared a global pandemic. Older adults have been found as a vulnerable group for developing severe forms of disease and increased mortality. The objective of the study was to propose a pathway to assist the decision-making process for hospital resource allocation for older adults with COVID-19 using simple geriatric assessment-based tools. We reviewed the available literature at this point of the COVID-19 outbreak, focusing in older adult care to extract key recommendations for those health-care professionals who will be treating older adults in the hospital emergency ward (HEW) in developing countries during the COVID-19 pandemic. We listed a series of easy recommendations for non-geriatrician doctors in the HEW and suggested simple tools for hospital resource allocation during critical care evaluation of older adults with COVID-19 in low- and middle-income countries. Age must not be used as the sole criterion for resource allocation among older adults with COVID-19. Simple and efficient tools are available to identify components of the comprehensive geriatric assessment, which could be useful to predict outcomes and provide high-quality care that would fit the particular needs of older adults in resource-limited settings amidst this global pandemic.


Maternal Perinatal Stress Trajectories and Negative Affect and Amygdala Development in Offspring.
Maternal psychological stress during pregnancy is a common risk factor for psychiatric disorders in offspring, but little is known about how heterogeneity of stress trajectories during pregnancy affect brain systems and behavioral phenotypes in infancy. This study was designed to address this gap in knowledge. Maternal anxiety, stress, and depression were assessed at multiple time points during pregnancy in two independent low-risk mother-infant cohorts (N=115 and N=2,156). Trajectories in maternal stress levels in relation to infant negative affect were examined in both cohorts. Neonatal amygdala resting-state functional connectivity MRI was examined in a subset of one cohort (N=60) to explore the potential relationship between maternal stress trajectories and brain systems in infants relevant to negative affect. Four distinct trajectory clusters, characterized by changing patterns of stress over time, and two magnitude clusters, characterized by severity of stress, were identified in the original mother-infant cohort (N=115). The magnitude clusters were not associated with infant outcomes. The trajectory characterized by increasing stress in late pregnancy was associated with blunted development of infant negative affect. This relationship was replicated in the second, larger cohort (N=2,156). In addition, the trajectories that included increasing or peak maternal stress in late pregnancy were related to stronger neonatal amygdala functional connectivity to the anterior insula and the ventromedial prefrontal cortex in the exploratory analysis. The trajectory of maternal stress appears to be important for offspring brain and behavioral development. Understanding heterogeneity in trajectories of maternal stress and their influence on infant brain and behavioral development is critical to developing targeted interventions.


Insulin Titration Guidelines for Patients With Type 1 Diabetes: It Is About Time!
A proposal that an Insulin Advisory Committee develop insulin titration guidelines 100 years after its discovery. Glucose control metrics remain poor despite significant advances in diabetes technology. A century after the introduction of insulin, health care providers and patients with type 1 diabetes have worldwide access to a variety of insulin delivery devices (IDDs), glucose monitors, bolus calculators (BCs), continuous glucose monitors (CGMs), and automated insulin delivery (AID) systems. However, these advances have not enabled most patients to achieve today's clear A1c and time-in-range goals. Much of this failure arises from the lack of clear insulin titration guidelines for determining appropriate insulin doses. The lack of dosing clarity results in local physicians, clinics, and individual patients managing insulin titrations as they see fit, creating significant inefficiencies for reaching recommended glycemic goals. This review (1) details the widespread problems generated by nonphysiological dose settings in today's BCs, insulin pumps, and AID systems; (2) presents a method to develop and implement optimized total daily doses of insulin to correct the most common problem of hyperglycemia; (3) discusses using large device databases to provide clear insulin titration guidelines that optimize BC settings from an optimized total daily dose (TDD) of insulin for patients with T1D; and (4) recommends the formation of an Insulin Advisory Committee to clarify the steps to take toward universal insulin titration guidelines, optimized BC settings, and a systematic logic for their use in insulin delivery devices.


Probiotics and Time to Achieve Full Enteral Feeding in Human Milk-Fed and Formula-Fed Preterm Infants: Systematic Review and Meta-Analysis.
Probiotics have been linked to a reduction in the incidence of necrotizing enterocolitis and late-onset sepsis in preterm infants. Recently, probiotics have also proved to reduce time to achieve full enteral feeding (FEF). However, the relationship between FEF achievement and type of feeding in infants treated with probiotics has not been explored yet. The aim of this systematic review and meta-analysis was to evaluate the effect of probiotics in reducing time to achieve FEF in preterm infants, according to type of feeding (exclusive human milk (HM) vs. formula). Randomized-controlled trials involving preterm infants receiving probiotics, and reporting on time to reach FEF were included in the systematic review. Trials reporting on outcome according to type of feeding (exclusive HM vs. formula) were included in the meta-analysis. Fixed-effect or random-effects models were used as appropriate. Results were expressed as mean difference (MD) with 95% confidence interval (CI). Twenty-five studies were included in the systematic review. In the five studies recruiting exclusively HM-fed preterm infants, those treated with probiotics reached FEF approximately 3 days before controls (MD -3.15 days (95% CI -5.25/-1.05), p = 0.003). None of the two studies reporting on exclusively formula-fed infants showed any difference between infants receiving probiotics and controls in terms of FEF achievement. The limited number of included studies did not allow testing for other subgroup differences between HM and formula-fed infants. However, if confirmed in further studies, the 3-days reduction in time to achieve FEF in exclusively HM-fed preterm infants might have significant implications for their clinical management.


Atopic dermatitis-like graft-versus-host disease treated with dupilumab.
The mainstay of treatment for atopic dermatitis (AD)-like graft-versus-host disease (GVHD) in both pediatric and adult patients includes oral corticosteroids with or without other systemic immunosuppressive therapies. To our knowledge, we report the first case series of dupilumab in the treatment of AD-like GVHD in a pediatric cohort of four patients, where we observed clinical improvement of GVHD as well as a reduction in itch in 3/4 (75%) patients. Our findings suggest that dupilumab is not only effective in treating AD-like GVHD, but also reduces systemic immunosuppression in the pediatric transplant population. The ability to reduce the length and amount of immunosuppression as well as improve quality of life suggest that dupilumab may serve as a safe and effective therapeutic option in our transplant population with GVHD.


Post-stroke fatigue and its dimensions within first 3 months after stroke.
Post-stroke fatigue (PSF) is a common stroke complication with long-term negative consequences. Assess the qualitative and quantitative PSF characteristics during 3 month post-stroke period. There were examined 141 patients with acute ischemic or hemorrhagic strokes at hospital stay, in 1, 2 and 3 months after stroke. PSF was measured by fatigue assessment scale (FAS), multidimensional fatigue inventory-20 (MFI-20) and fatigue severity scale (FSS). 116 (82.3%) patients had ischemic strokes, 25 (17.7%) had hemorrhagic strokes. According to FAS and MFI-20 "global fatigue" sub-scale, PSF was present, respectively, in 22.0% and 25.5% cases at hospital stay, in 38.3% and 35.5% cases in 3 month after stroke. The growing prevalence of PSF was based on significantly increasing the rates of PSD physical domain (from 28.4% to 41.1%) and the rates of PSF mental domain (from 19.1% to 31.9%). On the other hand, the rates of PSF activity-related component had been significantly reduced from 36.2% to 17.0% within observation period. Moreover, according to MFI-20, it had been revealed significant increasing of PSF intensities in global, physical and mental domains during first 3 post-stroke months. According to FSS value ranks, proportions of patients with "no PSF" had been decreased in 1.5 times due to simultaneously rising rates of "moderate" as well as "severe" PSF impacts on daily life. The PSF spreading is significantly increased during the first 3 post-stroke months due to increasing of rates and intensities of physical and mental PSF domains.


Repetitive Closed-Head Impact Model of Engineered Rotational Acceleration Induces Long-Term Cognitive Impairments with Persistent Astrogliosis and Microgliosis in Mice.
Repeated mild traumatic brain injury (rmTBI) has been identified by epidemiology as a high-risk factor for dementia at a later stage in life. Animal models to replicate complex features of human rmTBI and/or to evaluate long-term effects on brain function have not been established. In this study, we used a novel closed-head impact model of engineered rotational acceleration (CHIMERA) to investigate the long-term neuropathological and cognitive functional consequences of rmTBI. Adult C57BL/6 male mice were subjected to CHIMERA for 3 consecutive days 24 h apart. Functional outcomes were assessed by the beam walk and Morris water maze tests. Neuropathology was evaluated by immunostaining of glial fibrillary acidic protein (GFAP), amyloid precursor protein (APP), and ionizing calcium-binding adaptor molecule-1 (Iba-1), and by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or Western blotting of GFAP, Iba-1, and tumor necrosis factor (TNF)-α. Repeated CHIMERA (rCHIMERA) resulted in motor deficits at 3 days, and in learning and memory impairments that were sustained up to 6 months post injury. GFAP and TNF-α gene expression was increased within a week, whereas astrogliosis and microgliosis were induced starting from day 1 up to 6.5 months after rCHIMERA with upregulated GFAP and Iba-1 protein levels. rCHIMERA also induced APP deposition from day 1 to day 7, but this diminished by 1 month. In conclusion, rCHIMERA produces long-lasting cognitive impairments with astrogliosis and microgliosis in mice, suggesting that rCHIMERA can be a useful animal model to study the long-term complications, as well as the cellular and molecular mechanisms, of human rmTBI.


Stimulus functions in response chaining.
Behavior analysts have conceptualized chaining from two different positions: Position 1 (responses function as discriminative stimuli for subsequent responses) and Position 2 (responses produce stimuli that function as discriminative stimuli for subsequent responses). Twenty-four mentally retarded adults learned a chain of circuit board assembly responses consisting of placing resistors in the board and pressing switches. Lights came on after switch responses. After learning the chain, each subject was exposed to three experimental conditions (counterbalanced): (a) altered stimulus location, (b) altered stimulus sequence, and (c) missing stimulus. Although a clear test of Position 1 was not made, some support for Position 2 was obtained. Alternate interpretations were discussed.


SAMHD1 expression is a surrogate marker of immune infiltration and determines prognosis after neoadjuvant chemotherapy in early breast cancer.
The lack of validated surrogate biomarkers is still an unmet clinical need in the management of early breast cancer cases that do not achieve complete pathological response after neoadjuvant chemotherapy (NACT). Here, we describe and validate the use of SAMHD1 expression as a prognostic biomarker in residual disease in vivo and in vitro. SAMHD1 expression was evaluated in a clinical cohort of early breast cancer patients with stage II-III treated with NACT. Heterotypic 3D cultures including tumor and immune cells were used to investigate the molecular mechanisms responsible of SAMHD1 depletion through whole transcriptomic profiling, immune infiltration capacity and subsequent delineation of dysregulated immune signaling pathways. SAMHD1 expression was associated to increased risk of recurrence and higher Ki67 levels in post-NACT tumor biopsies of breast cancer patients with residual disease. Survival analysis showed that SAMHD1-expressing tumors presented shorter time-to-progression and overall survival than SAMHD1 negative cases, suggesting that SAMHD1 expression is a relevant prognostic factor in breast cancer. Whole-transcriptomic profiling of SAMHD1-depleted tumors identified downregulation of IL-12 signaling pathway as the molecular mechanism determining breast cancer prognosis. The reduced interleukin signaling upon SAMHD1 depletion induced changes in immune cell infiltration capacity in 3D heterotypic in vitro culture models, confirming the role of the SAMHD1 as a regulator of breast cancer prognosis through the induction of changes in immune response and tumor microenvironment. SAMHD1 expression is a novel prognostic biomarker in early breast cancer that impacts immune-mediated signaling and differentially regulates inflammatory intra-tumoral response.


Emotion dysregulation, symptoms, and interpersonal problems as independent predictors of a broad range of personality disorders in an outpatient sample.
Emotion dysregulation (ED) is considered a hallmark of borderline personality disorder and is prominent in other personality disorders (PDs). Its presence and contribution to personality pathology need to be explored in the whole range of PDs. In this study, we investigated the association of ED with the whole range of PD traits, symptoms, and interpersonal problems and then investigated whether ED had a unique contribution in predicting the different PDs. A sample of 478 treatment-seeking outpatients was interviewed with the SCID-II. The patients were then tested for symptoms (SCL-90-R), interpersonal problems (IIP-32), and ED (DERS). ED correlated with the large majority of PDs and with symptoms and interpersonal problems. Regression showed how ED explained a unique part of the variance for many PDs. ED appears to be a relevant feature of pathology in many PDs; with replication, it can be considered a treatment target in this population. Emotion dysregulation is present in many personality disorders. Emotion dysregulation is not just explained by heightened symptoms and interpersonal problems in personality disorders. Emotion dysregulation could be considered a treatment target in personality disorders other than borderline.


Carriage of multiresistant Streptococcus pneumoniae among children attending day-care centres in the Stockholm area.
To determine the prevalence of the asymptomatic carriage of drug-resistant Streptococcus pneumoniae (DRSP) by children attending day-care centres in the Stockholm area, nasopharyngeal swabs were cultured from 1129 children and 308 day-care personnel in 36 day-care centres during a 3-week period, from March to April 1995. Approximately 36% of the children were asymptomatic carriers of S. pneumoniae sensitive to penicillin and other antibiotics. The highest prevalence of nasopharyngeal carriage was found in the 2-year-old group (50%), whereas among the 4-year-old children colonization was observed in 42%, and among the 7-year-old children 21% were asymptomatic carriers of penicillin-sensitive S. pneumoniae. In 2 day-care centres, 4 and 5 children, respectively, were found to have DRSP strains in the nasopharynx. The same serotype of DRSP strain was found among the children attending the same day-care centre. During the same period, none of the staff were found to harbour DRSP in the nasopharynx, but 3% were asymptomatic carriers of penicillin-sensitive S. pneumoniae. The patterns of nasopharyngeal colonization by Haemophilus influenzae, Moraxella catarrhalis and Group A streptococci were also studied in 635 children during the same period. 42% of the nasal cultures yielded Moraxella, 32% H. influenzae and 2% Streptococcus pyogenes.


Feasibility of the transcatheter mitral valve repair for patients with severe mitral regurgitation and endangered heart failure.
The transcatheter edge-to-edge mitral valve repair using MitraClip has been a safe and effective treatment for severe mitral regurgitation (MR). In patients with severe MR and cardiogenic shock under hemodynamic supporting devices, emergent surgical mitral valve interventions carry extremely high risk for peri-operative morbidities and mortalities. The feasibility and efficacy of emergent MitraClip to rescue patients in critical conditions remains elucidate. Patients with severe MR and high or prohibitive surgical risks were referred for MitraClip procedures. Emergent MitraClip were conducted in patients with unstable hemodynamics and under mechanical or inotropic support. The hemodynamic measures, transthoracic echocardiography, transesophageal echocardiography, and blood tests were performed before MitraClip procedures. Procedural success was defined as having mild mitral regurgitation immediately after MitraClip, and patients were free from in-hospital mortality. Clinical and echocardiographic outcomes were followed by telephones and clinics. Among 50 consecutive patients (74.7 ± 11.2 years, 74% male), 8 emergent MitraClip procedures were conducted to rescue patients with cardiogenic shock. Extracorporeal membrane oxygenations were used in 2 patients and intra-aortic balloon pump were applied in 4 patients (50%). Compare to those who underwent elective procedures, patients underwent emergent MitraClip had higher surgical risk profile (EuroSCORE II 34.8% vs 5.1% and STS score 19.7% vs 5.1%), poorer renal function and higher right atrial pressure. There was no peri-procedural death, myocardial infarction, stroke or any adverse events requiring emergent cardiac surgery in both groups. Mild mitral regurgitation was achieved in 87.5% patients from the emergent group and 95.2% patients in the elective group (P = 0.514). The Kaplan-Meier analysis showed patients who underwent emergent procedures have poorer long-term survival rate as compare to those who received elective procedures. (P value = 0.008). When open-heart surgery is not feasible, trans-catheter mitral valve repair is an alternative way to rescue patients in cardiogenic shock status.


Incidental Finding of Cor Triatriatum Sinister in an Asymptomatic Woman With Ankylosing Spondylitis.
We present a 24-year-old woman with symptoms of backache, acute peripheral arthritis, joint swelling, and erythema, diagnosed with ankylosing spondylitis (AS) and determined to have cor triatriatum sinister (CTS) without cardiac symptoms. On physical examination, the patient had a rythmic S1 with a loud pulmonic component to her S2 and a grade 2/6 systolic murmur along the left sternal edge. Pulmonary examination was normal. Also her left knee and left metacarpophalangeal joints were swollen. Chest radiography revealed a slight prominence of the pulmonary arteries. Her echocardiogram showed a normal left ventricle and that the left atrium was divided into 2 distinct chambers by a membranous septum. In the left atrium, a moderately obstructive fibromuscular membrane was imaged, resulting in a transmembrane mean pressure gradient of 6 mm Hg. Pulmonary artery pressure was increased (peak systolic pulmonary pressure: 44 mm Hg). There was also mild mitral regurgitation and the atrial septum was intact. Cardiac MRI demonstrated CTS. Cardiovascular involvement is a common finding in patients with AS. Thus, careful cardiac evaluation appears to be mandatory in all cases of AS. Our case may be interesting in that to the best of our knowledge, AS with CTS has not been previously reported. Also a patient with CTS who has no cardiac symptoms is a very rare occurrence in the literature.


Serum Th1 (CXCL10) and Th2 (CCL2) chemokine levels in children with newly diagnosed Type 1 diabetes: a longitudinal study.
Cell-mediated immunity and pro-inflammatory cytokines are implicated in the pathogenesis of Type 1 diabetes. The aim of this study was to investigate whether circulating chemokines involved in T-helper 1 (CXCL10) and T-helper 2 (CCL2) autoimmunity are increased in children with Type 1 diabetes at onset and follow-up. Serum CXCL10 and CCL2 were measured in 96 children with newly diagnosed Type 1 diabetes, 59 age-matched first-degree relatives of diabetic children and 40 age-matched non-diabetic children with no family history of diabetes. In the diabetic children, an additional serum sample was obtained a median of 16 months after diagnosis. Serum CXCL10 levels were significantly higher in Type 1 children than in relatives or control children (P < 0.001); 44.7% of patients had a serum CXCL10 level >or= 2 standard deviation above the mean value of the control group vs. 3.4% of relatives (P < 0.0001). In contrast, serum CCL2 levels were similar in patients, relatives and control subjects. In the Type 1 diabetic patients at follow-up, CXCL10 was significantly reduced vs. baseline (P = 0.01), while CCL2 did not change. In children with newly diagnosed Type 1 diabetes, raised serum CXCL10 and normal CCL2 concentrations signal a predominant T-helper 1-driven autoimmune process, which shifts toward T-helper 2 immunity over the first 1-2 years from diagnosis.


Current antimicrobial management of community-acquired pneumonia in HIV-infected children.
Community-acquired pneumonia is a leading cause of morbidity and mortality amongst HIV-infected infants and children. Polymicrobial infection is common and, due to the difficulties in confirming the etiology of pneumonia, empiric broad-spectrum antimicrobial therapy is frequently used. The author based this article on literature identified from PubMed. The author's search terms included: pneumonia, community-acquired pneumonia, HIV, children. The articles reviewed included original studies, recent review articles and current guidelines on the management of pneumonia in HIV-infected children. The microbiological etiology and the empiric and pathogen-specific antimicrobial therapy of community-acquired pneumonia in HIV-infected and HIV-exposed infants and children are also discussed. There are many changing epidemiological factors impacting antimicrobial management of community-acquired pneumonia in the context of HIV infection in infants and children. These include vaccination strategies, antimicrobial prophylaxis, emerging drug-resistant pathogens, and recognition of the importance of viruses and tuberculosis in the etiology of community-acquired pneumonia. Further research is needed on optimal amtimicrobial management strategies in HIV-exposed uninfected children, and HIV-infected children receiving antiretroviral therapy.


Role of crystal field in mixed alkali metal effect: electron paramagnetic resonance study of mixed alkali metal oxyfluoro vanadate glasses.
The mixed alkali metal effect is a long-standing problem in glasses. Electron paramagnetic resonance (EPR) is used by several researchers to study the mixed alkali metal effect, but a detailed analysis of the nearest neighbor environment of the glass former using spin-Hamiltonian parameters was elusive. In this study we have prepared a series of vanadate glasses having general formula (mol %) 40 V2O5-30BaF2-(30 - x)LiF-xRbF with x = 5, 10, 15, 20, 25, and 30. Spin-Hamiltonian parameters of V(4+) ions were extracted by simulating and fitting to the experimental spectra using EasySpin. From the analysis of these parameters it is observed that the replacement of lithium ions by rubidium ions follows a "preferential substitution model". Using this proposed model, we were able to account for the observed variation in the ratio of the g parameter, which goes through a maximum. This reflects an asymmetric to symmetric changeover of the alkali metal ion environment around the vanadium site. Further, this model also accounts for the variation in oxidation state of vanadium ion, which was confirmed from the variation in signal intensity of EPR spectra.


Memory performance on the California Verbal Learning Test-II: findings from patients with focal frontal lesions.
Numerous studies have suggested that frontal cortex plays a strategic, rather than an absolute, role in memory performance. Typically, frontal patients are reported to have impaired recall but normal recognition memory. A recent meta-analysis, however, has questioned this conclusion. To further investigate the role of frontal cortex in long-term memory, patients with focal frontal lesions and age- and education-matched controls were tested on a new version of the California Verbal Learning Test (CVLT-II). Frontal patients exhibited a number of deficits on this test, including overall poorer recall, an increased tendency to make intrusions, reduced semantic clustering, and impaired yes/no recognition performance. Further analysis of the error rates in the yes/no recognition task revealed that frontal patients were most likely to mistakenly endorse 2 types of distractors: semantically related words and words from an interference list. These findings are discussed with respect to the role of frontal dysfunction in false recollections and poor source memory, as well as the distinction between the roles of frontal and temporal cortex in long-term memory.


Development of an imaging system for single droplet characterization using a droplet generator.
The spray droplets generated by agricultural nozzles play an important role in the application accuracy and efficiency of plant protection products. The limitations of the non-imaging techniques and the recent improvements in digital image acquisition and processing increased the interest in using high speed imaging techniques in pesticide spray characterisation. The goal of this study was to develop an imaging technique to evaluate the characteristics of a single spray droplet using a piezoelectric single droplet generator and a high speed imaging technique. Tests were done with different camera settings, lenses, diffusers and light sources. The experiments have shown the necessity for having a good image acquisition and processing system. Image analysis results contributed in selecting the optimal set-up for measuring droplet size and velocity which consisted of a high speed camera with a 6 micros exposure time, a microscope lens at a working distance of 43 cm resulting in a field of view of 1.0 cm x 0.8 cm and a Xenon light source without diffuser used as a backlight. For measuring macro-spray characteristics as the droplet trajectory, the spray angle and the spray shape, a Macro Video Zoom lens at a working distance of 14.3 cm with a bigger field of view of 7.5 cm x 9.5 cm in combination with a halogen spotlight with a diffuser and the high speed camera can be used.


miR-107 regulates cisplatin chemosensitivity of A549 non small cell lung cancer cell line by targeting cyclin dependent kinase 8.
Previous studies demonstrated that the acquired drug resistance of non-small cell lung cancer (NSCLC) was related to deregulation of miRNAs. However, the effects of miR-107 and the mechanism through which miR-107 affects the cisplatin chemoresistance in NSCLC have not been reported. TaqMan RT-PCR or Western blot assay was performed to detect the expression of mature miR-107 and cyclin dependent kinase 8 (CDK8) protein. The viabilities of treated cells were analyzed using MTT assay. We found that the expression level of miR-107 in A549 cells was significantly lower than that in normal human bronchial epithelial cells (0.45 ± 0.26 vs. 1.00 ± 0.29, P = 0.032). The MTT assay showed that the A549 cells transfected with miR-107 mimics were significantly more sensitive to the therapy of cisplatin than control cells. A549 cells transfected with miR-107 mimics showed a decreased CDK8 protein expression. Downregulation of CDK8 expression by siRNAs, A549 cells became more sensitive to the therapy of cisplatin. In addition, the enhanced growth-inhibitory effect by the miR-107 mimic transfection was enhanced after the addition of CDK8 siRNA. In conclusion, the present study provides the first evidence that miR-107 plays a key role in cisplatin resistance by targeting the CDK8 protein in NSCLC cell lines, suggesting that miR-107 can be used to predict a patient's response to chemotherapy as well as serve as a novel potential maker for NSCLC therapy.


[Expression and significance of cytokeratin 13 gene in oral squamous cell carcinoma].
To investigate the expression and its significance of cytokeratin 13 gene in oral squamous cell carcinoma (OSCC). Differential CK13 gene expression between 30 cases of paired normal and cancerous tissues were detected by reverse transcription-PCR (RT-PCR), and immunohistochemistry was conducted using monoclonal antibody against CK13 in them. The data were analyzed with SAS6.12 software for Fisher's exact test. RT-PCR results demonstrated that CK13 gene mRNA was upregulated in 27 cases of normal tissues than in paired cancerous samples, by 4.2-fold in total; and immunostain results revealed that expression of CK13 protein between normal oral squamous cell and OSCC, high differentiated OSCC and poor differentiated ones were significantly decreased (P<0.05). CK13 gene might play an important role in OSCC carcinogenesis and be regulated at post-transcriptional levels. Further research will contribute to confirm its role and mechanism.


Metabolic aspects of polycystic ovary syndrome.
The metabolic aberrations in patients with polycystic ovary syndrome (PCOS) demand a shift in clinical care from symptom driven to the prevention of chronic disease. The onset of carbohydrate intolerance or diabetes may be accelerated. The lipoprotein lipid profiles are compatible with the effects of insulin resistance. Disturbed cholesterol and triglyceride metabolism may eventuate in premature cardiovascular disease.


When to recognize that breastfeeding is not an option.
All members of the symposium panel agree that the best feeding option is exclusive breastfeeding. The benefits of breastfeeding are numerous, and the practice is advantageous to both mother and child. Yet, there are times when breastfeeding is not possible. As health care professionals, we need to realize when it is necessary to discuss feeding alternatives. We must make a point not to judge our patients in order to successfully educate parents about proper infant nutrition practices.


Invasive Ductal Carcinoma: Correlation of Immunophenotypic Features with Age.
To evaluate the frequency of hormone receptors and Her2neu expression and their correlation with age in patients of carcinoma breast. Descriptive, cross-sectional study. Department of Histopathology, Dr. Ziauddin Hospital, Karachi, between the period 2006 - 2013. Estrogen receptors, progesterone receptors and Her2neu immunohistochemical staining was performed on all specimens of carcinoma breast of female patients. Allred scoring was followed using normal epithelium as internal control. Age was determined in years. Results were described as percentages. Three hundred and forty-six cases of infiltrating ductal carcinoma of breast between the age of 20 - 90 years (mean= 49 ±14 years) were studied. Seventy-nine (23%) cases were below the age of 40 years. ER +ve cases were 210 (61%), PR +ve were 190 (55%), and 78 (23%) were Her2neu +ve. Three were 12 (3%) triple positive cases and 58 (17%) triple negative cases. One hundred and seven (31%) cases were ER/PR+ve and Her2neu -ve. Most of the breast cancer cases were aged between 41 - 50 years. Estrogen receptor positivity was maximum between 41 - 60 years. Fifty percent cases of carcinoma breast below 30-year age were also ER positive. A high proportion of breast cancer in young Pakistani females is alarming. Younger age harbours aggressive clinicopathologic characteristics. There is a due need for identifying high risk individuals/families including BRCA1 and BRCA2 testings, biologically driven trials devoted specifically to this group.


Motile cilia of human airway epithelia contain hedgehog signaling components that mediate noncanonical hedgehog signaling.
Differentiated airway epithelia produce sonic hedgehog (SHH), which is found in the thin layer of liquid covering the airway surface. Although previous studies showed that vertebrate HH signaling requires primary cilia, as airway epithelia mature, the cells lose primary cilia and produce hundreds of motile cilia. Thus, whether airway epithelia have apical receptors for SHH has remained unknown. We discovered that motile cilia on airway epithelial cells have HH signaling proteins, including patched and smoothened. These cilia also have proteins affecting cAMP-dependent signaling, including Gαi and adenylyl cyclase 5/6. Apical SHH decreases intracellular levels of cAMP, which reduces ciliary beat frequency and pH in airway surface liquid. These results suggest that apical SHH may mediate noncanonical HH signaling through motile cilia to dampen respiratory defenses at the contact point between the environment and the lung, perhaps counterbalancing processes that stimulate airway defenses.


The Sulfolobus solfataricus Lrp-like protein LysM regulates lysine biosynthesis in response to lysine availability.
Although the archaeal transcription apparatus resembles the eukaryal RNA polymerase II system, many bacterial-like regulators can be found in archaea. Particularly, all archaeal genomes sequenced to date contain genes encoding homologues of Lrp (leucine-responsive regulatory protein). Whereas Lrp-like proteins in bacteria are involved in regulation of amino acid metabolism, their physiological role in archaea is unknown. Although several archaeal Lrp-like proteins have been characterized recently, no target genes apart from their own coding genes have been discovered yet, and no ligands for these regulators have been identified so far. In this study, we show that the Lrp-like protein LysM from Sulfolobus solfataricus is involved in the regulation of lysine and possibly also arginine biosynthesis, encoded by the lys gene cluster. Exogenous lysine is the regulatory signal for lys gene expression and specifically serves as a ligand for LysM by altering its DNA binding affinity. LysM binds directly upstream of the TFB-responsive element of the intrinsically weak lysW promoter, and DNA binding is favored in the absence of lysine, when lysWXJK transcription is maximal. The combined in vivo and in vitro data are most compatible with a model in which the bacterial-like LysM activates the eukarya-like transcriptional machinery. As with transcriptional activation by Escherichia coli Lrp, activation by LysM is apparently dependent on a co-activator, which remains to be identified.


Advanced radiology utilization in a tertiary care emergency department from 2001 to 2010.
To evaluate the utilization trends of advanced radiology, i.e. computed tomography (CT) and magnetic resonance imaging (MRI), examination in an emergency department (ED) of an academic medical center from 2001 to 2010. We assessed the overall CT and MRI utilization, and the ED patient encounters. Each examination was evaluated according to the patient's age and anatomically relevant regions. During the study period, 737,760 patient visited the ED, and 156,287 CT and 35,018 MRI examinations were performed. The number of annual ED patients increased from 63,770 in 2001 to 94,609 in 2010 (P = 0.018). The rate of CT utilization increased from 105.5 per 1000 patient visits in 2001 to 289.2 in 2010 (P<0.001), and the rate of MRI utilization increased from 8.1 per 1000 patient visits in 2001 to 74.6 in 2010 (P<0.001). In all of the patient age groups, the overall CT and MRI utilization increased. The greater the patient age, the more likely the use of advanced radiology [CT: 87.1 per 1000 patients in age <20 vs. 293.9 per 1000 in age>60 (P<0.001); MRI: 5.1 per 1000 patients in age <20 vs. 108.7 per 1000 in age>60 (P<0.001)]. Abdomen-pelvis (40.2%) and the head (35.7%) comprised the majority of CT scans, while the head (86.4%) comprised the majority of MRI examinations. The rates of advanced radiology use increased across all anatomical regions, with the highest increase being in chest CT (5.9 per 1000 to 49.2) and head MRI (7.2 per 1000 to 61.9). We report a three-fold and nine-fold increase in the use of CT and MRI, respectively, during the study period. Additional studies will be required to understand the causes of this change and to determine the effect of advanced radiology utilization on the patient outcome.


Primary osteosarcoma of the ovary: a case report and literature review.
Pure osteosarcomas, in which this tumor is not the mesenchymal component of a biphasic tumor, are only rarely encountered in the ovary. Herein, we report a case of a pure ovarian osteoarcoma and review all previously reported cases of ovarian involvement by osteosarcoma in the English literature. The latter includes (with the present case) 6 cases of pure osteosarcoma (Group A), 5 cases of osteosarcoma arising from a teratoma (Group B), and 2 cases of osteosarcomas of osseous origin (humerus and maxilla) metastatic to the ovary (Group C). The average ages of the Groups A, B, and C patients were 52.6, 52, and 37.5 years, respectively. The average tumor sizes in these groups were 13.46, 13.82, and 16 cm, respectively. There was no statististically significant difference between the Group A and B patients with respect to tumor size (P = 0.94) or age (P = 0.96) (t test). Eight of the 11 patients in groups A and B were FIGO stage 3 or 4 at presentation. Five (83%) of the 6 group A patients and 2 (40%) of the 5 group B patients died of their disease an average of 4.8 and 3.5 months after initial evaluations respectively. However, the 2 patients who presented with stage 1 disease (and with follow-up information) have shown no evidence of tumor recurrence at an average of 26 months' follow-up. It is concluded that ovarian osteosarcomas are rare malignancies that are frequently associated with teratomas but may be seen in pure form. Unlike osseous osteosarcoma whose peak age of incidence is in the second decade, ovarian osteosarcomas occur at an older age group. Most patients have advanced stage disease at presentation. Ovarian osteosarcomas have a high (>60%) case fatality rate; analysis of the reported cases suggests that the latter is attributable to the advanced stage at which most patients present, as there are no reported cases of patients with stage 1 disease whose diseases have recurred after surgical resection or who have died of their disease.


Rational Design and Development of a Soluble Mesoporous Carrier for the Solidification of a Preconcentrated Self-Nanoemulsion Formulation.
The solidification of self-preconcentrated nanoemulsion without changes in nanodroplet formation gains particular consideration due to the interaction between solidified carriers. This work aimed to develop mannitol mesoporous as a soluble carrier for supersaturated self-nanoemulsion (SSNE) using a design of experiment (DoE) approach. The mesoporous carrier was prepared by a spray-drying technique. The type of templating agent (TA) used to form a porous system, the amount of TA, and solid loading in the spray-drying process were studied. Several characterizations were performed for mannitol mesoporous formation, namely, powder X-ray diffraction, thermal analysis, scanning electron microscopy, and surface area analyzer. Solidification of SSNE incorporated into the mesoporous mannitol was carried out, followed by compaction behavior, flowability, and nanodroplet formation. The results revealed several process parameters for preparing the mesoporous mannitol, notably TA, which gained more significant consideration. Solid loading in the mesoporous preparation system reduced the surface area and pore size and did not affect solid SSNE flowability. The amount of TA increased the pore size and volume dramatically as well as the compactibility and flowability. Ammonium carbonate was the preferable TA for preparing the mesoporous carrier, particularly for the nanodroplet formulation process. In addition, synergistic and antagonistic interactions between factors were also observed. The optimized mesoporous carrier was applied for solidification, and there was no difference between SSNE and solid SSNE in the performance of nanodroplet formation.


Organophosphate pesticide exposure and dialkyl phosphate urinary metabolites among chili farmers in northeastern Thailand.
Chlorpyrifos and profenofos are organophosphate pesticides (OPPs), we studied exposure and urinary metabolites in an agricultural area in the northeastern of Thailand during the chili-growing season (March - April) in 2012. This study was designed to assess pesticide exposure concentration through dermal and inhalation pathways and to find and depict a relationship between urinary metabolites and means of exposure. To estimate the pesticides exposure concentration, dermal wipes (hand, face, and feet), dermal patches and air samples were collected from 38 chili farmers. The morning void of pre and post application urine samples was an indicator of biological monitoring in the study which derived from 39 chili farmers. Chlorpyrifos and profenofos residues were detected on dermal patches, face wipes, and hand wipe samples, while no significant residues were found on the feet. Using a personal air sampling technique, all air samples detected pesticide residues. However, significant correlation between dermal pesticide exposure concentration and inhalation was not found (p>0.05). For urinary metabolite levels, there was a relationship between the first pre application morning void and post application morning void (p < 0.05); similar to the association between the first pre application morning void and the second post application morning void (p < 0.05). The main relationship between pesticide exposure and urinary metabolite was found to have been relevant to dermal exposure (r= 0.405; p < 0.05). The results of this study could suggested that public health education training programs, including the use of appropriate personal protective equipment (PPE), should be offered for the chili growing farmers in order to improve their ability to properly use pesticides. pesticide exposure, chili farmers, urinary metabolites, organophosphate pesticides.


Melanin-like Nanoparticles as an Alternative to Natural Melanin in Retinal Pigment Epithelium Cells and Their Therapeutic Effects against Age-Related Macular Degeneration.
Melanin is a natural pigment that is widely distributed in many parts of the human body, such as the skin and retinal pigment epithelium (RPE) in eyes. In contrast to skin melanin, which is being constantly synthesized by the epidermal melanocytes, melanin in the RPE does not regenerate. Melanin is known to function as a potential radical scavenger and photoprotective agent. However, the protective effects of melanin against oxidative stress decline with increasing age. This phenomenon has been correlated with the pathogenesis of age-related macular degeneration (AMD). To increase the potential antioxidant and photoprotective characteristics of melanin, we designed a therapeutic strategy for replenishment of melanin using PEGylated synthetic melanin-like nanoparticles (MNPs) in the RPE for the treatment of AMD. We performed experiments using AMD-like cellular and mouse models and demonstrated that MNPs are biocompatible and selectively target reactive oxygen species (ROS) with powerful antioxidant properties. MNPs can traffic and accumulate in the RPE and are exclusively located in cytosol, but not the nucleus and mitochondria of the cells, for at least 3 months after a single-dose intravitreal injection. Our findings demonstrate that MNPs are able to substitute for natural melanin in the RPE and suggest the potential efficacy of MNPs as a natural radical scavenger against oxidative stress in ROS-related diseases, such as AMD.


One primer to rule them all: universal primer that adds BBa_B0034 ribosomal binding site to any coding standard 10 BioBrick.
Here, we present a universal, simple, efficient, and reliable way to add small BioBrick parts to any BioBrick via PCR that is compatible with BioBrick assembly standard 10. As a proof of principle, we have designed a universal primer, rbs_B0034, that contains a ribosomal binding site (RBS; BBa_B0034) and that can be used in PCR to amplify any coding BioBrick that starts with ATG. We performed test PCRs with rbs_B0034 on 31 different targets and found it to be 93.6% efficient. Moreover, when supplemented with a complementary primer, addition of RBS can be accomplished via whole plasmid site-directed mutagenesis, thus reducing the time required for further assembly of composite parts. The described method brings simplicity to the addition of small parts, such as regulatory elements to existing BioBricks. The final product of the PCR assembly is indistinguishable from the standard or 3A BioBrick assembly.


The sensory experiences of adults with autism spectrum disorder: A qualitative analysis.
It has been well established that individuals with autism spectrum disorder report unusual experiences with sensory stimuli compared with typically developing individuals. However, there is a paucity of research exploring the nature of such experiences. A focus group was conducted with six adults with a diagnosis of autism or Asperger syndrome. Data were coded and analysed using an inductive, qualitative thematic analysis. Four main themes encompassing both positive and negative sensory experiences emerged from these data: (a) the importance of particular aspects of stimuli in their perception, (b) the importance of having control over stimuli, (c) how emotions/mental states could impact/be impacted by sensory stimuli, and (d) physical responses to stimuli. These data are discussed alongside extant literature. Limitations, possible implications, and potential directions of future research are also discussed.


Lanthanide-dependent alcohol dehydrogenases require an essential aspartate residue for metal coordination and enzymatic function.
The lanthanide elements (Ln3+), those with atomic numbers 57-63 (excluding promethium, Pm3+), form a cofactor complex with pyrroloquinoline quinone (PQQ) in bacterial XoxF methanol dehydrogenases (MDHs) and ExaF ethanol dehydrogenases (EDHs), expanding the range of biological elements and opening novel areas of metabolism and ecology. Other MDHs, known as MxaFIs, are related in sequence and structure to these proteins, yet they instead possess a Ca2+-PQQ cofactor. An important missing piece of the Ln3+ puzzle is defining what features distinguish enzymes that use Ln3+-PQQ cofactors from those that do not. Here, using XoxF1 MDH from the model methylotrophic bacterium Methylorubrum extorquens AM1, we investigated the functional importance of a proposed lanthanide-coordinating aspartate residue. We report two crystal structures of XoxF1, one with and another without PQQ, both with La3+ bound in the active-site region and coordinated by Asp320 Using constructs to produce either recombinant XoxF1 or its D320A variant, we show that Asp320 is needed for in vivo catalytic function, in vitro activity, and La3+ coordination. XoxF1 and XoxF1 D320A, when produced in the absence of La3+, coordinated Ca2+ but exhibited little or no catalytic activity. We also generated the parallel substitution in ExaF to produce ExaF D319S and found that this variant loses the capacity for efficient ethanol oxidation with La3+ These results provide evidence that a Ln3+-coordinating aspartate is essential for the enzymatic functions of XoxF MDHs and ExaF EDHs, supporting the notion that sequences of these enzymes, and the genes that encode them, are markers for Ln3+ metabolism.


Present views on toxidynamics of soman poisoning.
This paper summarizes present views on effects of soman (O-pinacolyl methylphosphonofluoridate) and on possibilities of treatment of intoxication with this highly toxic compound. Simultaneously, it indicates the problems need to be solved. On this base only, it will be possible to improve the therapy of soman intoxication which is not sufficiently effective at present.


Cows Come Down from the Mountains before the (Mw = 6.1) Earthquake Colfiorito in September 1997; A Single Case Study.
The September-October 1997 seismic sequence in the Umbria-Marche regions of Central Italy has been one of the stronger seismic events to occur in Italy over the last thirty years, with a maximum magnitude of Mw = 6.1. Over the last three years, a collection of evidence was carried out regarding non-seismic phenomena, by interviewing local residents using a questionnaire. One particular observation of anomalous animal behaviour, confirmed by many witnesses, concerned a herd of cows, which descended from a mountain close to the streets of a village near the epicentre, a few days before the main shock. Testimonies were collected using a specific questionnaire including data on earthquake lights, spring variations, human diseases, and irregular animal behaviour. The questionnaire was compiled after the L'Aquila earthquake in 2009, and was based upon past historical earthquake observations. A possible explanation for the cows' behavior-local air ionization caused by stress-activated positive holes-is discussed.


High-performance meta-absorber for the surface wave under the spoof surface plasmon polariton mode.
Perfect absorbers are highly desired in many engineering and military applications, including radar cross section (RCS) reduction, cloaking devices, and sensor detectors. However, most types of present absorbers can only absorb space propagation waves, yet absorption for the surface wave (SW) has not been researched intensively. In reality, when the space wave illuminates on the metal under large oblique angles, surface waves can be excited on the interface between metal and dielectric and thus would increase the RCS and influence the stealth performance. Here, based on the wave vector and impedance matching theories, we propose a broadband absorber for the surface wave under spoof surface plasmon polariton (SSPP) mode. The former theory ensures that surface waves can enter the absorber efficiently, and the latter guarantees perfect absorption. The experimental results indicate that our absorber can achieve a broadband (9.4-18 GHz) performance with an absorption ratio better than 90%, which is in great agreement with the simulations. Therefore, our device can be applied in RCS reduction for the metal devices, antenna array decoupling and many other applications. Also, this work provides a unique methodology to design new types of broadband surface wave absorbers.


Identification and expression profile analysis of odorant binding proteins in the oriental fruit fly Bactrocera dorsalis.
Olfaction is crucial in many insects for critical behaviors, including those regulating survival and reproduction. Insect odorant-binding proteins (OBPs) function in the first step of the olfactory system and play an essential role in the perception of odorants, such as pheromones and host chemicals. The oriental fruit fly, Bactrocera dorsalis, is a destructive fruit-eating pest, due to its wide host range of up to 250 different types of fruits and vegetables, and this fly causes severe economic damage to the fruit and vegetable industry. However, OBP genes have not been largely identified in B. dorsalis. Based on our previously constructed B. dorsalis cDNA library, ten OBP genes were identified in B. dorsalis for the first time. A phylogenetic tree was generated to show the relationships among the 10 OBPs of B. dorsalis to OBP sequences of two other Dipteran species, including Drosophila melanogaster and the mosquito Anopheles gambiae. The expression profiles of the ten OBPs in different tissues (heads, thoraxes, abdomens, legs, wings, male antennae and female antenna) of the mated adults were analyzed by real-time PCR. The results showed that nine of them are highly expressed in the antenna of both sexes, except BdorOBP7. Four OBPs (BdorOBP1, BdorOBP4, BdorOBP8, and BdorOBP10) are also enriched in the abdomen, and BdorOBP7 is specifically expressed in leg, indicating that it may function in other biological processes. This work will provide insight into the roles of OBPs in chemoreception and help develop new pest-control strategies.


Malignant spinal cord compression in cancer patients may be mimicked by a primary spinal cord tumour.
Although it is quite rare, second primary neoplasms in cancer patients may present with the signs and symptoms of malignant spinal cord compression. Primary spinal cord tumours in the cancer patients may be deceptive and considered as the recurrent first cancer. Therefore, it should be precisely differentiated and appropriately managed. We report such a case of intramedullary ependymoma of the cervical spinal cord mimicking metatstatic recurrent lymphoma and causing cord compression. A 50-year-old man developed intramedullary ependymoma of the cervical spinal cord 1.5 years following chemoradiation for Waldeyer's ring lymphoma. He presented with a 2-month history of neck pain, progressive upper- and lower-extremity numbness and weakness, and bowel and bladder dysfunction. Magnetic resonance imaging revealed an intramedullary expansive lesion extending from C4 to C6 levels of the cervical spinal cord. The clinical and radiological findings were suggestive of malignant process. A comprehensive investigation failed to detect another site of disease. He underwent operation, and the tumour was subtotally resected. The patient's neurological deficits improved subsequently. The development of the intramedullary ependymoma following treating lymphoma has not been reported. We describe the clinical, radiological and pathological findings of this case and review the literature.


[66% glucose, a safe sclerosant. Experimental study].
Although accidents due to the intra-arterial injection of detergent sclerosant are very rarely observed, they are dramatic in their effects and often result in amputations, a risk accepted with difficulty for a treatment with a functional aim. To avoid these incidents, which may occur even when treatment is applied by the most experienced surgeons, the authors have used 66% glucose solution without accident since 1948. To confirm efficacy of the method, an experimental study compared 66% glucose (66 G) with a very commonly used product, 1% sodium tetradecyl sulfate (STD), in the rabbit. Except when enormous doses of 66 G are employed, the only effect noted was eosinophilic necrosis of the vessel wall without clinical symptoms, whereas doses eight times lower of STD produced an irreversible ischemia from obliterating endarteritis of the branches of the vascular tree injected. The 66% glucose solution appears to be a very safe, gently acting sclerosant, and the product of choice for peri- and post-operative sclerosis, particularly in regions where accidental arterial puncture is anatomically possible.


Genetic diversity of chloroquine-resistant Plasmodium vivax parasites from the western Brazilian Amazon.
The molecular basis of Plasmodium vivax chloroquine (CQ) resistance is still unknown. Elucidating the molecular background of parasites that are sensitive or resistant to CQ will help to identify and monitor the spread of resistance. By genotyping a panel of molecular markers, we demonstrate a similar genetic variability between in vitro CQ-resistant and sensitive phenotypes of P. vivax parasites. However, our studies identified two loci (MS8 and MSP1-B10) that could be used to discriminate between both CQ-susceptible phenotypes among P. vivax isolates in vitro. These preliminary data suggest that microsatellites may be used to identify and to monitor the spread of P. vivax-resistance around the world.


Stress-dependent and -independent expression of the myogenic regulatory factors and the MARP genes after eccentric contractions in rats.
The relationship between muscle mechanical conditions and gene expression was investigated by varying both stress and contraction mode imposed upon rat dorsiflexors (n= 25), activating them at high or low frequencies (150 Hz or 40 Hz) either eccentrically or isometrically. Muscle physiological, immunohistochemical and gene expression changes were then measured 24 h after the exercise bout. Peak stress was the best predictor of muscle injury, independent of contraction mode (i.e. eccentric or isometric). When peak stresses were matched, no physiological or immunohistochemical differences were detected between isometric and eccentric contractions. The expression of certain myogenic regulatory and muscle ankyrin repeat protein (MARP) genes (myoD, myogenin, MLP and CARP) depended both on peak muscle stress achieved during contraction and contraction mode. In contrast, Arpp/Ankrd2 was dramatically upregulated only by eccentric contractions, but not by isometric contractions, even though the stress level of the eccentric contractions varied over a three-fold range and overlapped with that of the isometric group. The role that Arpp/Ankrd2 upregulation plays in the biological response to eccentric contraction remains to be determined, as does the control mechanism whereby the expression of certain genes (such as myoD, myogenin, MLP and CARP) is sensitive to muscle stress while another (Arpp/Ankrd2) is sensitive only to contraction mode.


Correlation of endoscopic disease severity with pediatric ulcerative colitis activity index score in children and young adults with ulcerative colitis.
To investigate of pediatric ulcerative colitis activity index (PUCAI) in ulcerative colitis correlate with mucosal inflammation and endoscopic assessment of disease activity (Mayo endoscopic score). We reviewed charts from ulcerative colitis patients who had undergone both colonoscopy over 3 years. Clinical assessment of disease severity within 35 d (either before or after) the colonoscopy were included. Patients were excluded if they had significant therapeutic interventions (such as the start of corticosteroids or immunosuppressive agents) between the colonoscopy and the clinical assessment. Mayo endoscopic score of the rectum and sigmoid were done by two gastroenterologists. Inter-observer variability in Mayo score was assessed. We identified 99 patients (53% female, 74% pancolitis) that met inclusion criteria. The indications for colonoscopy included ongoing disease activity (62%), consideration of medication change (10%), assessment of medication efficacy (14%), and cancer screening (14%). Based on PUCAI scores, 33% of patients were in remission, 39% had mild disease, 23% had moderate disease, and 4% had severe disease. There was "moderate-substantial" agreement between the two reviewers in assessing rectal Mayo scores (kappa = 0.54, 95%CI: 0.41-0.68). Endoscopic disease severity (Mayo score) assessed by reviewing photographs of pediatric colonoscopy has moderate inter-rater reliability, and agreement was less robust in assessing patients with mild disease activity. Endoscopic disease severity generally correlates with clinical disease severity as measured by PUCAI score. However, children with inflamed colons can have significant variation in their reported clinical symptoms. Thus, assessment of both clinical symptoms and endoscopic disease severity may be required in future clinical studies.


Robotic-Assisted Urologic Surgery in Infants: Positioning, Trocar Placement, and Physiological Considerations.
Pediatric robotic-assisted laparoscopic procedures are becoming increasingly common. They have been shown to be safe in younger patients, including infants. Successful adoption of robotic-assisted surgery in infants requires an understanding of the technical factors unique to this patient population. This review will delineate the specific considerations to safely perform robotic-assisted laparoscopic procedures in infants, including physiological changes associated with pneumoperitoneum in infants, positioning, trocar placement, and docking.